Selection for bacterial genes that are specifically induced in host tissues: The hunt for virulence factors

A broadly applicable new approach, termed IVET, has been devised that allows the positive selection of bacterial genes that are specifically induced in host tissues. A subset of these ivi genes should encode virulence factors, the functions of which are specifically required for the infection process. Indeed, we have shown that genes identified using the IVET system are induced in animal tissues and that mutations in such genes confer a defect in virulence. The IVET methodology has several applications in the area of vaccine and antimicrobial drug development. This technique was designed for the identification of virulence factors and thus may lead to the discovery of new antigens useful as vaccine components. The IVET system facilitates the isolation of mutations in genes that play a part in virulence and, thus, may assist in the construction of live attenuated vaccines. In addition, the identification of ivi promoters provides a method to establish in vivo regulated expression of heterologous antigens in live vaccines. Last, the identification of ivi genes offers insights into the changes in metabolism, gene regulation, and cell-surface properties that occur during growth of microbes in animal tissues. The elucidation of these gene products should provide new targets for antimicrobial drug development.